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et aI., 1991b; Larsson et aI., 1990). In colon cancer Vogelstein et al. (1989) found in about
30% of the tumors loss of chromosome 22q. Miyaki et al.(1990) showed that chromosome
22 loss in colorectal cancer is a relatively late event. Less than 5% of the adenomas from
FAP patients showed loss of chromosome 22, whereas 33% of invasive carcinomas revealed
this loss. So far, mutations in the NF2 gene were observed in 1/69 breast tumors, 6/20
primary and melanoma metaslases, and 2/64 coloreclal carcinomas (Bianchi et aI., 1994;
Arakawa et aI., 1994) and 118 ependymomas (Rubio et aI., 1994). However, 5
pheochromocytomas and 30 aslrocylomas did not reveal mutations in this gene (Bianchi et
aI., 1994). Furlher sludy is required to elucidale whether the above mentioned genes andlor
other chromosome 22 specific genes are involved in the pathogenesis these tumors.
4.8 Chromosome 22
Chromosome 22 is the second smallest acrocentric chromosome, comprising approximately
56 Mb or 1.9% of Ihe haploid genome (Morton, 1991). The shorl arm (22p) only harbours
the ribosomal genes of the nucleolar organizer region, while Ihe long arm (22q) represents
the bulk of the chromosomal DNA. The long ann of the chromosome is involved in a
number of diseases. These include Di George syndrome, velo-cardia-facial syndrome, cat eye
syndrome and a number of cancers such as chronic myelocylic leukemia, Burkililymphoma,
Ewing sarcoma, meningiomas and vestibular schwannomas (McDermid et aI., 1993). The
past few years a lot of efforl has been put into Ihe genomic characterization of chromosome
22. This was facilitated by Ihe development of high-resolulion panels of somalic cell hybrids,
detailed linkage maps and the isolation of a large number of chromosome 22 specific DNA
markers (Duman ski et aI., 1990b; Budarf et aI., 1991; Delallre et aI., 1991; Dumanski et aI.,
1991; Fiedler et aI., 1991; Emanuel et aI., 1991; Frazer et aI., 1992; van Biezen et aI.,
1993; Emanuel et aI., 1993). Very helpful in the construclion of a genomic contig of this
chromosome is the availability of chromosome 22 specific cosmid libraries (de Jong et aI.,
1989). These cosmid and genomic YAC libraries have resulted in the isolation of a contig
of about 1100 kb on human chromosome 22ql2 (Xie et aI., 1993). Very recently a physical
map became available for 22qll-ql2 using pulsed-field gel electrophoresis. This long-range
restriction map spans approximately 11 Mb of DNA (McDermid et aI., 1993).
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